| RRC ID |
84357
|
| Author |
Kato K, Noda T, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, Tomimaru Y, Takahashi H, Uemura M, Asaoka T, Shimizu J, Doki Y, Eguchi H.
|
| Title |
KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation.
|
| Journal |
Cancer Sci
|
| Abstract |
Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.
|
| Volume |
115(5)
|
| Pages |
1520-1535
|
| Published |
2024-5-1
|
| DOI |
10.1111/cas.16144
|
| PMID |
38475666
|
| PMC |
PMC11093189
|
| MeSH |
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation*
Colonic Neoplasms* / genetics
Colonic Neoplasms* / metabolism
Colonic Neoplasms* / pathology
Endothelial Cells* / metabolism
Endothelial Cells* / pathology
Female
Humans
Kallikreins* / genetics
Kallikreins* / metabolism
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Liver Neoplasms* / pathology
Liver Neoplasms* / secondary
Male
Mice
Mice, Inbred BALB C
Neovascularization, Pathologic / metabolism
Neovascularization, Pathologic / pathology
Tumor Microenvironment
|
| IF |
4.966
|
| Resource |
| Human and Animal Cells |
Colon-26(RCB2657) |
